Structural Determinants of the Stability of Enzyme‐Responsive Polyion Complex Nanoparticles Targeting Pseudomonas aeruginosa’s Elastase

Abstract

Here, we report how the stability of polyion complex (PIC) particles containing Pseudomonas aeruginosa’s elastase (LasB) degradable peptides and antimicrobial poly(ethylene imine) is significantly improved by careful design of the peptide component. Three LasB‐degradable peptides are reported herein, all of them carrying the LasB‐degradable sequence −GLA− and for which the number of anionic amino acids and cysteine units per peptide were systematically varied. Our results suggest that while net charge and potential to cross‐link via disulfide bond formation do not have a predictable effect on the ability of LasB to degrade these peptides, a significant effect of these two parameters on particle preparation and stability is observed. A range of techniques has been used to characterize these new materials and demonstrates that increasing the charge and cross‐linking potential of the peptides results in PIC particles with better stability in physiological conditions and upon storage. These results highlight the importance of molecular design for the preparation of PIC particles and should underpin the future development of these materials for responsive drug delivery.

Design of Colloidally Stable and Non‐Toxic Petox‐Based Polymersomes for Cargo Molecule Encapsulation

“…The radius of gyration ( R g ) values of PEtOx 36 ‐ b ‐PLA 100 PEtOx 46 ‐ b ‐PLA 100 and PEtOx 62 ‐ b ‐PLA 100 polymersomes were determined as 89.50, 92.27 and 111.14 nm respectively, via static light scattering analyses. The ratio of R g / R h is a morphologic assessment which is used to distinguish the shape of the polymeric assemblies . When the R g / R h ratios of PEtOx‐ b ‐PLA self‐assemblies evaluated, it is found to be between 0.91–0.93 which are in accordance with previous findings and fits to the theoretical value (1.0) for vesicles…”

Stimuli‐Responsive Delivery of Antimicrobial Peptides Using Polyelectrolyte Complexes

“…[102] Delivery from both surfaces and nanoparticulate systems have been developed, and these systems have been used to target a range of bacteria including some of the most virulent and antibiotic-resistant pathogens such as S. aureus [102] and P. aeruginosa. [75,76] The release of the AMP in many of these systems is triggered at low pH, as the anionic polyelectrolytes are neutralized at that pH, which results in weakened electrostatic interactions, which hold the polyelectrolyte complexes together. These materials may therefore be suitable for intracellular delivery of AMPs, targeting pathogens that commonly traffic through the endosomes such as M. tuberculosis and Listeria monocytogenes.…”

“…Using similar principles to those discussed above, Fernandez-Trillo and colleagues developed highly selective polyelectrolyte complex nanoparticles by combining a peptide that could be degraded by LasB (a protease secreted by pathogen P. aeruginosa) with cationic antimicrobial polymer polyethyleneimine. [75,76] Glutamic acids were incorporated into C, D, E) Adapted with permission. [66] Copyright 2013 Wiley-VCH, A) Adapted with permission under terms of the Creative Commons CC-BY 4.0 license.…”

Polyelectrolyte-multivalent molecule complexes: physicochemical properties and applications

“…162 The overexpression of certain enzymes in specific environments can be exploited to generate intelligent PEMMCs. [165][166][167][168][169] Gupta and coworkers exploited the susceptibility of poly-L-lysine to biodegradation by proteolytic enzymes to build proteaseresponsive PEMMCs (Fig. 13c).…”